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Query: faculty: "FNWI" and publication year: "2012"

Author M.A. Boks Title Modulation of immune tolerance: the role of tolerogenic dendritic cells and TNFα Promotor S.M. van Ham Co-promotors J.A. ten Brinke, J.J. Zwaginga Date 26-10-2012 Year 2012 Pages 149 ISBN 978-94-6182-153-9 Faculty Faculty of Science Institute/dept. FNWI: Swammerdam Institute for Life Sciences (SILS) Keywords tolerance induction; anti-TNFα-biologicals; regulatory T cells; IL-10; tolerogenic dendritic cells Abstract This thesis describes the role of tolerogenic DC and anti-TNFα agents in tolerance induction. IL-10-generated tDC potently induce Treg, while inhibiting CD4+ T cell proliferation and cytokine production by Th1 and Th2 cell subsets. Anti-TNFα shares this dual function; inducing IL-10 production and a regulatory phenotype and function in naïve CD4+ T cells, and at the same time counteracting CD4+ effector T cell priming by inhibiting activation status, survival and IFNγ production. Anti-TNFα upregulates inhibitory molecules galectin-3, legumain, GARP and LAG-3 which may be involved in (cell contact-dependent) suppressive function, as is described for natural Treg. In addition, chemokine and chemokine receptor expression are altered after TNFα neutralization, suggesting a change in chemoattraction by Treg and chemotaxis of Treg, thereby regulating the encounter with other immune cells. The picture emerges that tDC and anti-TNFα agents synergistically enhance immune suppression. Combination therapy of tDC and anti-TNFα agents may therefore improve tolerance induction therapy in patients with TNFα-mediated inflammatory diseases such as rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, multiple sclerosis and inflammatory bowel diseases. Language English Document type Dissertation Download papers Thesis     Front cover Title pages Contents Chapter 1: General introduction Chapter 2: An optimized CFSE-based T-cell suppression assay to evaluate the suppressive capacity of regulatory T-cells induced by human tolerogenic dendritic cells Chapter 3: IL-10-generated tolerogenic dendritic cells are optimal for functional regulatory T cell induction: a comparative study of human clinical-applicable DC Chapter 4: Inhibition of TNFα signalling by anti-TNFα primes naïve CD4+ T cells towards IL-10+ cells with strong regulatory phenotype and function   Chapter 5: CD4+ T cells co-expressing IL-10 and IFNγ display a regulatory gene profile and dampen immune responses   Chapter 6: Summarizing discussion Nederlandse samenvatting Curriculum vitae Dankwoord Document finder Use this url to link to this page: http://dare.uva.nl/en/record/429159 Contact us about this recordNotify a colleague Add to bookbag

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